Key result
GLP-1 receptor agonists delay MACE by ~0.6 months over 48 months versus control.
Why the study?
To evaluate the time-varying cardio-protective effect of GLP-1RAs using pooled data from contemporary cardiovascular outcome trials using the difference in restricted mean survival time as the effect estimate.
Does glucagon-like peptide-1 receptor agonist therapy delay the occurrence of major adverse cardiovascular events in patients with type 2 diabetes mellitus?
Meta-Analysis (n=60,080)
Yes
Does glucagon-like peptide-1 receptor agonist therapy delay the occurrence of major adverse cardiovascular events in patients with type 2 diabetes mellitus?
Mean Difference: 0.63 (95% CI 0.27–0.98)
p-value: p=<0.001
GLP-1 receptor agonists delay the occurrence of major adverse cardiovascular events in patients with type 2 diabetes by an average of 0.63 months over 4 years, providing an easily understandable absolute measure of treatment benefit.
GLP-1RAs provide a modest absolute MACE delay in type 2 diabetes; extends RCT evidence with RMST quantification of time-to-event benefit.
AIMS: To evaluate the time-varying cardio-protective effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) using pooled data from eight contemporary cardiovascular outcome trials using the difference in the restricted mean survival time (ΔRMST) as the effect estimate. MATERIAL AND METHODS: Data from eight multinational cardiovascular outcome randomized controlled trials of GLP-1RAs for type 2 diabetes mellitus were pooled. Flexible parametric survival models were fit from published Kaplan-Meier plots. The differences between arms in RMST (ΔRMST) were calculated at 12, 24, 36 and 48 months. ΔRMST values were pooled using an inverse variance-weighted random-effects model; heterogeneity was tested with Cochran's Q statistic. The endpoints studied were: three-point major adverse cardiovascular events (MACE), all-cause mortality, stroke, cardiovascular mortality and myocardial infarction. RESULTS: We included eight large (3183-14 752 participants, total = 60 080; median follow-up range: 1.5 to 5.4 years) GLP-1RA trials. Among GLP-1RA recipients, we observed an average delay in three-point MACE of 0.03, 0.15, 0.37 and 0.63 months at 12, 24, 36 and 48 months, respectively. At 48 months, while cardiovascular mortality was comparable in both arms (pooled ΔRMST 0.163 [-0.112, 0.437]; P = 0.24), overall survival was higher (ΔRMST = 0.261 [0.08-0.43] months) and stroke was delayed (ΔRMST 0.22 [0.15-0.33]) in patients receiving GLP-1RAs. CONCLUSIONS: Glucagon-like peptide-1 receptor agonists may delay the occurrence of MACE by an average of 0.6 months at 48 months, with meaningfully larger gains in patients with cardiovascular disease. This metric may be easier for clinicians and patients to interpret than hazard ratios, which assume a knowledge of absolute risk in the absence of treatment.
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Deo et al. (2022) conducted a meta-analysis in Type 2 diabetes mellitus (n=60,080). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) vs. Control was evaluated on Three-/four-point major adverse cardiovascular events (MACE) at 48 months (ΔRMST 0.63 months, 95% CI 0.27-0.98, p=<0.001). Glucagon-like peptide-1 receptor agonists significantly delayed the occurrence of major adverse cardiovascular events by an average of 0.63 months at 48 months compared to control.
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